Inhibition of breast cancer metastasis to the lungs with UBS109.

Synthetic monocarbonyl analogs of curcumin (MACs) are cytotoxic against several cancers including head and neck cancer, pancreatic cancer, colon cancer, and breast cancer. Mechanisms of action include depolarization of the mitochondrial membrane potential and inhibition of NF-κB, leading to apoptosis. We previously demonstrated that UBS109 (MAC), has preventive effects on bone loss induced by breast cancer cell lines.

Metabolism of a G protein-coupled receptor modulator, including two major 1,2,4-oxadiazole ring-opened metabolites and a rearranged cysteine-piperazine adduct.

Metabolites of a G protein-coupled receptor modulator containing 1,2,4-oxadiazole and piperazine substructures were identified in vitro in human, rat, and dog hepatocyte incubates and in vivo in rat plasma, bile, urine, and feces by using 14C-radiolabeled parent compound. Exposure coverage for the major circulating metabolites in humans at steady state and in preclinical species used in drug safety assessments was determined by using pooled plasma samples collected from a human multiple ascending dose study and a 3-month rat toxicokinetic study. Metabolites M1 and M2, which were formed by opening of the 1,2,4-oxadiazole ring, were observed as major metabolites both in vitro and in vivo across species.

Expression and characterization of dog cytochrome P450 2A13 and 2A25 in baculovirus-infected insect cells.

Dog CYP2A13 and CYP2A25 were coexpressed with dog NADPH-cytochrome P450 reductase (OR) in baculovirus-infected Sf9 insect cells. CYP2A13 effectively catalyzed 7-ethoxycoumarin (7EC) deethylation and coumarin hydroxylation with apparent K(m) values of 4.8 and 2.